Background and objective
The availability of chest computed tomography (CT) imaging can help diagnose comorbidities associated with chronic obstructive pulmonary disease (COPD). Their systematic ...identification and relationship with all‐cause mortality have not been explored. Furthermore, whether their CT‐detected prevalence differs from clinical diagnosis is unknown.
Methods
The prevalence of 10 CT‐assessed comorbidities was retrospectively determined at baseline in 379 patients (71% men) with mild to severe COPD attending pulmonary clinics. Anthropometrics, smoking history, dyspnoea, lung function, exercise capacity, BODE (BMI, Obstruction, Dyspnoea and Exercise capacity) index and exacerbations rate were recorded. The prevalence of CT‐determined comorbidities was compared with that recorded clinically. Over a median of 78 months of observation, the independent association with all‐cause mortality was analysed. A ‘CT‐comorbidome’ graphically expressed the strength of their association with mortality risk.
Results
Coronary artery calcification, emphysema and bronchiectasis were the most prevalent comorbidities (79.8%, 62.7% and 33.9%, respectively). All were underdiagnosed before CT. Coronary artery calcium (hazard ratio HR 2.09; 95% CI 1.03–4.26, p = 0.042), bronchiectasis (HR 2.12; 95% CI 1.05–4.26, p = 0.036) and low psoas muscle density (HR 2.61; 95% CI 1.23–5.57, p = 0.010) were independently associated with all‐cause mortality and helped define the ‘CT‐comorbidome’.
Conclusion
This study of COPD patients shows that systematic detection of 10 CT‐diagnosed comorbidities, most of which were not detected clinically, provides information of potential use to patients and clinicians caring for them.
This multicentric study shows that chest computed tomography (CT) to evaluate the presence of 10 comorbidities detects important pathologies not diagnosed in the clinical management of those patients. While emphysema, coronary artery calcification (CAC) and bronchiectasis were the most prevalent CT‐detected comorbidities, CAC, bronchiectasis and low Psoas muscle density were independently associated with all‐cause mortality.
See related Editorial
Abstract
Rationale and objective
Patients with chronic obstructive pulmonary disease (COPD), usually diagnosed after the 6th decade, frequently suffer from comorbidities. Whether COPD patients ...50 years or younger (Young COPD) have similar comorbidities with the same frequency and mortality impact as aged-matched controls or older COPD patients is unknown.
Methods
We compared comorbidity number, prevalence and type in 3 groups of individuals with ≥ 10 pack-years of smoking: A Young (
≤
50 years) COPD group (n = 160), an age-balanced control group without airflow obstruction (n = 125), and Old (> 50 years) COPD group (n = 1860). We also compared survival between the young COPD and control subjects. Using Cox proportional model, we determined the comorbidities associated with mortality risk and generated Comorbidomes for the “Young” and “Old” COPD groups.
Results
The severity distribution by GOLD spirometric stages and BODE quartiles were similar between Young and Old COPD groups. After adjusting for age, sex, and pack-years, the prevalence of subjects with at least one comorbidity was 31% for controls, 77% for the Young, and 86% for older COPD patients. Compared to controls, “Young” COPDs’ had a nine-fold increased mortality risk (p < 0.0001). “Comorbidomes” differed between Young and Old COPD groups, with tuberculosis, substance use, and bipolar disorders being distinct comorbidities associated with increased mortality risk in the Young COPD group.
Conclusions
Young COPD patients carry a higher comorbidity prevalence and mortality risk compared to non-obstructed control subjects. Young COPD differed from older COPD patients by the behavioral-related comorbidities that increase their risk of premature death.
Obstructive sleep apnoea (OSA) is associated with pharyngeal inflammation, but the coexistence of systemic inflammation is controversial. This study investigated whether local and systemic ...inflammatory biomarkers are related in patients with OSA. An uncontrolled extension to the study assessed the response to effective treatment.We recruited 89 patients with OSA (apnoea/hypopnoea index (AHI) ≥5 events·h
), 28 snorers and 26 healthy controls. Pharyngeal lavage (PHAL) and plasma samples were collected at baseline and after a 1-year follow-up. Inflammatory cells were evaluated by flow cytometry; interleukin (IL)-6, IL-8 and tumour necrosis factor-α were evaluated by immunoassay.In PHAL, CD4
T-cells, IL-6 and IL-8 were higher in OSA patients than in snorers or healthy controls (p<0.05). The AHI correlated with CD4
, IL-6 and IL-8 in PHAL (all p-values <0.05). There were no differences in the inflammatory biomarkers in plasma between the study groups and no relationship between plasma and PHAL biomarkers. Biomarkers decreased significantly in PHAL but not in plasma after 1 year of therapy with continuous positive airway pressure or surgery.In patients with OSA, increased levels of inflammatory biomarkers were found in PHAL, which were reduced with effective treatment. No simultaneous increase in plasma inflammatory biomarkers was found.
The value of the single-breath diffusing capacity of the lungs for carbon monoxide (Dlco) relates to outcomes for patients with COPD. However, little is known about the natural course of Dlco over ...time, intersubject variability, and factors that may influence Dlco progression.
What is the natural course of Dlco in patients with COPD over time, and which other factors, including sex differences, could influence this progression?
We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including Dlco, was monitored annually over 5 years. A random coefficients model was used to evaluate Dlco changes over time.
The mean (± SE) yearly decline in Dlco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant Dlco % slope annual decline (4.14%/y). At baseline, women with COPD had lower Dlco values (11.37% ± 2.27%; P < .001) in spite of a higher FEV
% than men. Compared with men, women with COPD had a steeper Dlco annual decline of 0.89% ± 0.42%/y (P = .039).
Patients with COPD have an accelerated decline in Dlco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in Dlco values in women, compared with men, suggests a differential impact of sex in gas exchange function.
ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.
Abstract
Background
Hypoxia can reduce the levels of soluble receptor for advanced glycation end-products (sRAGE), a new anti-inflammatory biomarker of COPD. We assessed sRAGE in patients with ...hypoxia-related diseases such as COPD, OSA and OSA-COPD overlap.
Methods
Plasma levels of sRAGE were measured in 317 subjects at baseline (57 heathy nonsmokers HNS, 84 healthy smokers HS, 79 OSA, 62 COPD and 35 OSA-COPD overlap patients) and in 294 subjects after one year of follow-up (50 HNS, 74 HS, 77 OSA, 60 COPD and 33 overlap).
Results
After adjusting for age, sex, smoking status and body mass index, sRAGE levels showed a reduction in OSA (− 12.5%,
p
= 0.005), COPD (− 14.8%,
p
< 0.001) and OSA-COPD overlap (− 12.3%,
p
= 0.02) compared with HNS. There were no differences when comparing sRAGE plasma levels between overlap patients and those with OSA or COPD alone. At follow-up, sRAGE levels did not change significantly in healthy subjects, COPD and OSA or OSA-COPD overlap nontreated with continuous positive airway pressure (CPAP). Moreover, in patients with OSA and OSA-COPD overlap who were treated with CPAP, sRAGE increased significantly.
Conclusions
The levels of sRAGE are reduced in COPD and OSA. Treatment with CPAP appears to improve sRAGE levels in patients with OSA who also had COPD.
Epigenetic changes in obstructive sleep apnea (OSA) have been proposed as a mechanism for end-organ vulnerability. In children with OSA, Forkhead Box P3 (FOXP3) DNA methylation were associated with ...inflammatory biomarkers; however, the methylation pattern and its effect in the expression of this gene have not been tested in adults with OSA.
Plasma samples from subjects without comorbid conditions other than OSA were analyzed (the Epigenetics Status and Subclinical Atherosclerosis in Obstructive Sleep Apnea (EPIOSA) Study: NCT02131610). In 16 patients with severe OSA (Apnea-Hypopnea Index-AHI- > 30 events/h) and seven matched controls (AHI < 5), methylation of FOXP3 gen was evaluated by PCR of the promoter and by pyrosequencing of the intron 1 Treg-specific demethylated region (TSDR). In another 74 patients with OSA (AHI > 10) and 31 controls, we quantified FOXP3 protein expression by ELISA and gene expression by quantitative real-time PCR. C-reactive protein (CRP) and plasma Treg cells were also evaluated.
Neither the levels of the promoter nor the TSDR demethylated region were different between controls and patients with OSA, whether they were grouped by normal or high CRP. FOXP3 protein and mRNA expression did not differ between groups.
FOXP3 methylation or its expression is not altered in adults with OSA, whatever their inflammatory status.
Obstructive sleep apnea (OSA) patients are at special risk of suffering atherosclerosis, leading to major cardiovascular diseases. Notably, the transforming growth factor (TGF-β) plays a crucial role ...in the development and progression of atherosclerosis. In this context, the central regulator of TGF-β pathway, SMAD4 (small mother against decapentaplegic homolog 4), has been previously reported to be augmented in OSA patients, which levels were even higher in patients with concomitant cardiometabolic diseases. Here, we analyzed soluble and intracellular SMAD4 levels in plasma and monocytes from OSA patients and non-apneic subjects, with or without early subclinical atherosclerosis (eSA). In addition, we used in vitro and ex vivo models to explore the mechanisms underlying SMAD4 upregulation and release. Our study confirmed elevated sSMAD4 levels in OSA patients and identified that its levels were even higher in those OSA patients with eSA. Moreover, we demonstrated that SMAD4 is overexpressed in OSA monocytes and that intermittent hypoxia contributes to SMAD4 upregulation and release in a process mediated by NLRP3. In conclusion, this study highlights the potential role of sSMAD4 as a biomarker for atherosclerosis risk in OSA patients and provides new insights into the mechanisms underlying its upregulation and release to the extracellular space.
People with pre-existing lung diseases such as chronic obstructive pulmonary disease (COPD) are more likely to get very sick from SARS-CoV-2 disease 2019 (COVID-19). Still, an interrogation of the ...immune response to COVID-19 infection, spatially throughout the lung structure, is lacking in patients with COPD. For this study, we characterized the immune microenvironment of the lung parenchyma, airways, and vessels of never- and ever-smokers with or without COPD, all of whom died of COVID-19, using spatial transcriptomic and proteomic profiling. The parenchyma, airways, and vessels of COPD patients, compared to control lungs had (1) significant enrichment for lung-resident CD45RO
memory CD4
T cells; (2) downregulation of genes associated with T cell antigen priming and memory T cell differentiation; and (3) higher expression of proteins associated with SARS-CoV-2 entry and primary receptor ubiquitously across the ROIs and in particular the lung parenchyma, despite similar SARS-CoV-2 structural gene expression levels. In conclusion, the lung parenchyma, airways, and vessels of COPD patients have increased T-lymphocytes with a blunted memory CD4 T cell response and a more invasive SARS-CoV-2 infection pattern and may underlie the higher death toll observed with COVID-19.
Obstructive sleep apnea (OSA) is a worldwide highly prevalent disease associated with systemic consequences, including excessive sleepiness, impairment of neurocognitive function and daytime ...performance, including driving ability. The long-term sequelae of OSA include and increase risk for cardiovascular, cerebrovascular and metabolic syndrome disorders that ultimately lead to premature death if untreated. To ensure optimal long-term outcomes, the assessment and management of OSA should be personalized with the involvement of the appropriate specialist. Most studies have demonstrated inmediate improvement in daytime somnolence and quality of life with CPAP and other therapies, but the effect of long-term treatment on mortality is still under debate. Currently, the long-term management of OSA should be based on a) identifying physiological or structural abnormalities that are treatable at the time of patient evaluation and b) comprehensive lifestyle interventions, especially weight-loss interventions, which are associated with improvements in OSA severity, cardiometabolic comorbidities, and quality of life. In long-term management, attention should be paid to the clinical changes related to a potential reoccurrence of OSA symptoms and it is also necessary to monitor throughout the follow up how the main associated comorbidities evolve.
Chronic obstructive pulmonary disease (COPD) comprises distinct phenotypes, all characterised by airflow limitation.
We hypothesised that somatotype changes - as a surrogate of adiposity - from early ...adulthood follow different trajectories to reach distinct phenotypes.
Using the validated Stunkard's Pictogram, 356 COPD patients chose the somatotype that best reflects their current body build and those at ages 18, 30, 40 and 50 years. An unbiased group-based trajectory modelling was used to determine somatotype trajectories. We then compared the current COPD-related clinical and phenotypic characteristics of subjects belonging to each trajectory.
At 18 years of age, 88% of the participants described having a lean or medium somatotype (estimated body mass index (BMI) between 19 and 23 kg·m
) while the other 12% a heavier somatotype (estimated BMI between 25 and 27 kg·m
). From age 18 onwards, five distinct trajectories were observed. Four of them demonstrating a continuous increase in adiposity throughout adulthood with the exception of one, where the initial increase was followed by loss of adiposity after age 40. Patients with this trajectory were primarily females with low BMI and
(diffusing capacity of the lung for carbon monoxide). A persistently lean trajectory was seen in 14% of the cohort. This group had significantly lower forced expiratory volume in 1 s (FEV
),
, more emphysema and a worse BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) score thus resembling the multiple organ loss of tissue (MOLT) phenotype.
COPD patients have distinct somatotype trajectories throughout adulthood. Those with the MOLT phenotype maintain a lean trajectory throughout life. Smoking subjects with this lean phenotype in early adulthood deserve particular attention as they seem to develop more severe COPD.
PDF
